Karen Badellino is a registered nurse with advanced clinical experience and significant skills in basic science research. The goal of this application is to structure a transition from basic science to translational research by acquisition of more advanced abilities in biostatistics and independence in patient-oriented research as an Assistant Professor of Nursing and Investigator in the School of Medicine. The University of Pennsylvania provides an excellent environment for research, with many core facilities and expert resources. Dr. Badellino will be mentored by Dr. Daniel Rader, an expert in the field of lipid metabolism and renowned for translational research. Her long-term career goal is to establish an independent area of patient-oriented translational research and to mentor other nurses seeking similar careers. The focus of the research project is endothelial lipase (EL), a member of the triglyceride lipase family that has been shown, in mouse over expression studies, to markedly deplete plasma HDL levels and may have a significant role in human lipoprotein metabolism. The amount and activity of EL in human plasma is not known. The global hypothesis is that EL, by hydrolyzing lipoprotein-associated phospholipids, decreases the size of HDL, producing a proatherogenic plasma lipid profile. The three specific aims are: 1: To test the hypothesis that levels of EL mass in human plasma are correlated with lipoprotein levels. 2: To test the hypothesis that EL activity in human plasma inversely correlates with HDL levels and positively correlates with atherosclerosis. 3: To test the hypothesis that there is a difference in EL mass in individuals with either hypertriglyceridemia, high LDL-C or high HDL-C compared to normal controls. To test the hypothesis that increased EL mass will correlate positively with LDL particle size and inversely with HDL particle size. The methods used to address these questions include recruitment of subjects with various lipid disorders, ELISA, triglyceride and phospholipase assays, NMR analysis of lipoproteins and evaluation of coronary artery calcification scores.